Racemic bupivacaine is an effective long-acting anaesthetic, and may be given as an epidural. However, racemic bupivacaine is cardiotoxic, having depressant electrophysiological and mechanical effects on the heart. It should therefore be used with caution in cardiac-compromised patients, and the use of high doses and high concentrations is contraindicated.
In particular, bupivacaine has produced death in a number of patients, including women in childbirth and when used in the Bier's block technique. Although the incidence of death has been relatively small, the concern has been sufficient to stop the use of 0.75% bupivacaine for obstetrics and the proscribing of bupivacaine for use in Bier's blocks.
In addition, due to its mode of action, directly on the nervous system, at higher doses, bupivacaine is known to have undesirable central nervous system (CNS) side-effects which, prima facie, are connected to its anaesthetic activity. Indeed, the occurrence of CNS side-effects is one of the major factors limiting the use of this drug in normal clinical practice employing techniques such as local infiltration, nerve block, field block, epidural and spinal blocks.
It has been suggested that levobupivacaine is less cardiotoxic than dextrobupivacaine and racemic bupivacaine. See, for example, Vanhoutte et al, Br. J. Pharmacol. 103: 1275-1281 (1991), and Denson et al, Regional Anaesthesia, 17: 311-316 (1992). However, these reports are based on work in vitro, and cannot necessarily be extrapolated to any mammals, and certainly not to humans.
The surprising and effective utility of levobupivacaine in man, in vivo, is evidenced for the first time in WO-A-9510276, WO-A-9510277 and Gristwood et al, Exp. Opin. Invest. Drugs 3 (11): 1209-12 (1994).
No long-acting anaesthetic is approved for use in paediatrics. Children are particularly concerned about surgery, making the control of anaesthesia a particular problem. A relatively narrow therapeutic window is available. Further, there is a potential problem with intubation, because of the small airway and associated risk of damage. Children have relatively undeveloped livers, therefore increasing the risk that there will be drug interaction. All these problems mean that long-acting general anaesthetics are not registered for use in paediatrics.
Because a child is in development, and has growing/dividing cells, a particular concern in using any drugs on a child is their long-term effect. It is therefore desirable to avoid the use of drugs that may have genotoxic properties, especially if the drugs are to be used often and over a prolonged period.